PLoS ONE (Jan 2011)

The E3 ubiquitin ligase activity of Trip12 is essential for mouse embryogenesis.

  • Masashi Kajiro,
  • Mai Tsuchiya,
  • Yoh-Ichi Kawabe,
  • Ryohei Furumai,
  • Naoya Iwasaki,
  • Yuki Hayashi,
  • Miyuki Katano,
  • Yuka Nakajima,
  • Natsuka Goto,
  • Tatsuya Watanabe,
  • Akiko Murayama,
  • Hisashi Oishi,
  • Masatsugu Ema,
  • Satoru Takahashi,
  • Hiroyuki Kishimoto,
  • Junn Yanagisawa

DOI
https://doi.org/10.1371/journal.pone.0025871
Journal volume & issue
Vol. 6, no. 10
p. e25871

Abstract

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Protein ubiquitination is a post-translational protein modification that regulates many biological conditions. Trip12 is a HECT-type E3 ubiquitin ligase that ubiquitinates ARF and APP-BP1. However, the significance of Trip12 in vivo is largely unknown. Here we show that the ubiquitin ligase activity of Trip12 is indispensable for mouse embryogenesis. A homozygous mutation in Trip12 (Trip12(mt/mt)) that disrupts the ubiquitin ligase activity resulted in embryonic lethality in the middle stage of development. Trip12(mt/mt) embryos exhibited growth arrest and increased expression of the negative cell cycle regulator p16. In contrast, Trip12(mt/mt) ES cells were viable. They had decreased proliferation, but maintained both the undifferentiated state and the ability to differentiate. Trip12(mt/mt) ES cells had increased levels of the BAF57 protein (a component of the SWI/SNF chromatin remodeling complex) and altered gene expression patterns. These data suggest that Trip12 is involved in global gene expression and plays an important role in mouse development.